Bones support the body's soft tissues and body weight and protect the internal organs from external shocks by enclosing them. Moreover, bones are one of the important parts of the body that not only support muscles or organs but also store calcium or other essential minerals, such as phosphorus or magnesium, in the body.
There is a joint between bones that constitute the body. Joints can be classified into immovable joints with little or no mobility between two bones or cartilages that contact each other, such as skull or dental root, movable joints with many connective tissues and high mobility between two bones such as an animal's limb bones or jawbone, and amphiarthrodial joints. Joints generally refer to the movable joints, and the movable joints are classified into syndesmoses where both bones are connected only by ligaments and synovial joints. The synovial joint refers to a joint surrounded by a connective tissue capsule (articular capsule). The inside of the articular capsule secretes a lubricating fluid called synovial fluid, and many ligaments are located outside the articular capsule to strengthen the joint.
Cartilaginous tissue surrounds a joint and absorbs the force of joint movement. When the cartilaginous tissue is damaged, arthritis accompanied by swelling, fever, and pain is caused. Arthritis occurs regardless of race, and it is divided into more than 100 groups depending on the cause. The most common form is osteoarthritis, which is a degenerative joint disease that is mainly caused by aging, and others include rheumatoid arthritis and psoriatic arthritis, which are autoimmune diseases, and infectious septic arthritis. In particular, degenerative arthritis is generally a disease of the elderly, mainly caused by aging of the joints, but is also caused by a combination of various factors, such as genetic factors, nutritional imbalance, lack of exercise, excessive exercise or injury, wrong actions or attitudes that put a strain on the joints such as excessive labor, overload due to obesity, etc., and thus also occurs frequently in young people. As such, arthritis is a disease with a high incidence in a wide range of ages, but the damaged tissues are not naturally regenerated or restored, which limit social activities of patients for a long time and deteriorate the quality of life.
Traditionally, studies of autografting, allografting, and artificial bone grafting have been performed to treat arthritis; however, such treatments are known to have problems including complications such as infection, hematoma, etc. at the bone harvest site (autografting), the risks of disease transmission from donors (allografting), and no bone formation (artificial bone grafting).
Moreover, conservative therapies such as exercise therapy including weight control, diet therapy, injection therapy, and drug therapy, tissue regeneration therapies, and surgical therapies such as artificial joint replacement used in severe cases are also used for the treatment of arthritis.
However, exercise therapy has the effect of strengthening the surrounding tissues to delay additional symptoms, but does not fundamentally regenerate damaged tissues, and it is difficult to perform due to pain when the symptoms are severe.
Moreover, the injection of hyaluronic acid (HA), a lubricating component of the joint, is used to reduce the friction of damaged sites, thereby alleviating pain and preventing symptoms from worsening. Furthermore, for the purpose of alleviating inflammation and pain, aspirin, acetaminophen, or several nonsteroidal antiinflammatory drugs (NSAIDs) and steroidal drugs such as cortisone have been used. However, these drug therapies are not the fundamental treatment for repairing damaged tissues and are reported to damage the stomach, tissue, and bone due to side effects during long-term use, resulting in a need for additional validation.
If the above-mentioned conservative therapies are not effective or if severe pain persists, a surgical therapy to replace the damaged joint with an artificial joint is used; however, the life of the artificial joint is limited to about 10 years, and thus reoperation is needed if necessary. In this case, the difficulty in removal of the artificial joint fixed to the bone, the necessity to transplant a larger artificial joint, and the necessity of extensive surrounding bone tissues put restrictions on the reoperation. Due to these problems, more attention should be paid when applying the artificial joint replacement to young people.
With the recent development of artificial cell culture techniques, a method of artificially culturing and implantation of chondrocytes from multipotent stem cells or mesenchymal stem cells has been reported. However, it is not easy to obtain sufficient autologous cells, and in terms of adhesion, regeneration efficiency, and safety of transplanted cells, there are still many technical and cost problems to be solved for many patients.
With the advent of an aging society, the population of the elderly suffering from arthritis is steadily increasing, and joint diseases caused by excessive exercise, nutritional imbalance, obesity, etc. are also increasing in young people. Accordingly, there is a continuing need for new therapeutic agents applicable to various arthritic diseases; however, there has been no report of new therapeutic agents that can regenerate cartilaginous tissue damaged by arthritis, inhibit apoptosis of chondrocytes, and exhibit the effect of stem cell therapy, and thus there is still a need for developing such therapeutic agents.